Hypercalcemic and Hyperphosphatemic Actions of Dihydrotachysterol, Vitamin D2and Hytakerol (AT-10) in Rats and in Dogs

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Abstract
The hypercalcemic and hyperphosphatemic effects of equivalent dosages of crystalline dihydrotachysterol (DHT), Hytakerol (AT-10) and vitamin D2 are reported. In rats, DHT at high levels was more toxic than Hytakerol or vitamin D2. It produced marked hypercalcemia, hyperphosphatemia and high serum urea nitrogen levels, the latter probably on the basis of renal damage. In dogs, the onset and decline of hypercalcemia with orally administered DHT was very rapid, requiring only 3 days for maximal effect or for return to control levels upon discontinuance. On a weight basis, Hytakerol was less potent, with a more gradual decline upon cessation of administration, and vitamin D2 produced the least hypercalcemia, which, however, persisted for over 3 weeks after the vitamin was discontinued. The hypercalcemic sterol in Hytakerol (identified physicochemically as dihydrovitamin D2-II in a previous report) is 1/5 to 1/6 as potent as its isomer, DHT. The inadequacy of serum calcium levels as a measure of relative potencies of hypercalcemic sterols is discussed.

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